1.Protective Effect of Administered Rolipram against Radiation-Induced Testicular Injury in Mice.
Wan LEE ; Yeonghoon SON ; Hyosun JANG ; Min Ji BAE ; Jungki KIM ; Dongil KANG ; Joong Sun KIM
The World Journal of Men's Health 2015;33(1):20-29
PURPOSE: Pelvic irradiation for the treatment of cancer can affect normal cells, such as the rapidly proliferating spermatogenic cells of the testis, leading to infertility, a common post-irradiation problem. The present study investigated the radioprotective effect of rolipram, a specific phosphodiesterase type-IV inhibitor known to increase the expression and phosphorylation of the cyclic adenosine monophosphate response element-binding protein (CREB), a key factor for spermatogenesis, with the testicular system against pelvic irradiation. MATERIALS AND METHODS: Male C57BL/6 mice were treated with pelvic irradiation (2 Gy) and rolipram, alone or in combination, and were sacrificed at 12 hours and 35 days after irradiation. RESULTS: Rolipram protected germ cells from radiation-induced apoptosis at 12 hours after irradiation and significantly increased testis weight compared with irradiation controls at 35 days. Rolipram also ameliorated radiation-induced testicular morphological changes, such as changes in seminiferous tubular diameter and epithelial height. Additionally, seminiferous tubule repopulation and stem cell survival indices were higher in the rolipram-treated group than in the radiation group. Moreover, rolipram treatment counteracted the radiation-mediated decrease in the sperm count and mobility in the epididymis. CONCLUSIONS: These protective effects of rolipram treatment prior to irradiation may be mediated by the increase in pCREB levels at 12 hours post-irradiation and the attenuated decrease in pCREB levels in the testis at 35 days post-irradiation in the rolipram-treated group. These findings suggest that activation of CREB signaling by rolipram treatment ameliorates the detrimental effects of acute irradiation on testicular dysfunction and the related male reproductive functions in mice.
Adenosine Monophosphate
;
Animals
;
Apoptosis
;
Cyclic AMP Response Element-Binding Protein
;
Epididymis
;
Germ Cells
;
Humans
;
Infertility
;
Male
;
Mice*
;
Phosphorylation
;
Rolipram*
;
Seminiferous Tubules
;
Sperm Count
;
Spermatogenesis
;
Stem Cells
;
Testis
2.beta-irradiation (166Ho patch)-induced skin injury in mini-pigs: effects on NF-kappaB and COX-2 expression in the skin.
Joong Sun KIM ; Kyung Jin RHIM ; Won Seok JANG ; Sun Joo LEE ; Yeonghoon SON ; Seung Sook LEE ; Sunhoo PARK ; Sang Moo LIM
Journal of Veterinary Science 2015;16(1):1-9
In the present study, the detrimental effect of beta-emission on pig skin was evaluated. Skin injury was modeled in mini-pigs by exposing the animals to 50 and 100 Gy of beta-emission delivered by 166Ho patches. Clinicopathological and immunohistochemical changes in exposed skin were monitored for 18 weeks after beta-irradiation. Radiation induced desquamation at 2~4 weeks and gradual repair of this damage was evident 6 weeks after irradiation. Changes in basal cell density and skin depth corresponded to clinically relevant changes. Skin thickness began to decrease 1 week after irradiation, and the skin was thinnest 4 weeks after irradiation. Skin thickness increased transiently during recovery from irradiation-induced skin injury, which was evident 6~8 weeks after irradiation. Epidermal expression of nuclear factor-kappa B (NF-kappaB) differed significantly between the untreated and irradiated areas. One week after irradiation, cyclooxygenase-2 (COX-2) expression was mostly limited to the basal cell layer and scattered among these cells. High levels of COX-2 expression were detected throughout the full depth of the skin 4 weeks after irradiation. These findings suggest that NF-kappaB and COX-2 play roles in epidermal cell regeneration following beta-irradiation of mini-pig skin.
Animals
;
Cyclooxygenase 2/genetics/*metabolism
;
*Holmium
;
Male
;
NF-kappa B/genetics/*metabolism
;
Radiation Injuries, Experimental/metabolism/*veterinary
;
Skin/metabolism/*radiation effects
;
Swine
;
Swine, Miniature
3.Therapeutic effect of topical application of curcumin during treatment of radiation burns in a mini-pig model.
Joongsun KIM ; Sunhoo PARK ; Byung Suk JEON ; Won Seok JANG ; Sun Joo LEE ; Yeonghoon SON ; Kyung Jin RHIM ; Soong In LEE ; Seung Sook LEE
Journal of Veterinary Science 2016;17(4):435-444
Curcumin protects the skin against radiation-induced epidermal damage and prevents morphological changes induced by irradiation skin, thereby maintaining the epidermal thickness and cell density of basal layers. In this study, the effects of topical curcumin treatment on radiation burns were evaluated in a mini-pig model. Histological and clinical changes were observed five weeks after radiation exposure to the back (⁶⁰Co gamma-radiation, 50 Gy). Curcumin was applied topically to irradiated skin (200 mg/cm²) twice a day for 35 days. Curcumin application decreased the epithelial desquamation after irradiation. Additionally, when compared to the vehicle-treated group, the curcumin-treated group showed reduced expression of cyclooxygenase-2 and nuclear factor-kappaB. Furthermore, irradiation prolonged healing of biopsy wounds in the exposed area, whereas curcumin treatment stimulated wound healing. These results suggest that curcumin can improve epithelial cell survival and recovery in the skin and therefore be used to treat radiation burns.
Biopsy
;
Burns*
;
Cell Count
;
Curcumin*
;
Cyclooxygenase 2
;
Epithelial Cells
;
Radiation Exposure
;
Skin
;
Wound Healing
;
Wounds and Injuries
4.Chronic Treatment with Combined Chemotherapeutic Agents Affects Hippocampal Micromorphometry and Function in Mice, Independently of Neuroinflammation.
Sohi KANG ; Sueun LEE ; Juhwan KIM ; Jong Choon KIM ; Sung Ho KIM ; Yeonghoon SON ; Taekyun SHIN ; BuHyun YOUN ; Joong Sun KIM ; Hongbing WANG ; Miyoung YANG ; Changjong MOON
Experimental Neurobiology 2018;27(5):419-436
Chemotherapeutic agents induce long-term side effects, including cognitive impairment and mood disorders, particularly in breast cancer survivors who have undergone chemotherapy. However, the precise mechanisms underpinning chemotherapy-induced hippocampal dysfunction remain unknown. In this study, we investigated the detrimental effects of chronic treatment with a combination of adriamycin and cyclophosphamide (AC) on the neuronal architecture and functions of the hippocampi of female C57BL/6 mice. After chronic AC administration, mice showed memory impairment (measured using a novel object recognition memory task) and depression-like behavior (measured using the tail suspension test and forced swim test). According to Golgi staining, chronic AC treatment significantly reduced the total dendritic length, ramification, and complexity as well as spine density and maturation in hippocampal neurons in a sub-region-specific manner. Additionally, the AC combination significantly reduced adult neurogenesis, the extent of the vascular network, and the levels of hippocampal angiogenesis-related factors. However, chronic AC treatment did not increase the levels of inflammation-related signals (microglial or astrocytic distribution, or the levels of pro-inflammatory cytokines or M1/M2 macrophage markers). Thus, chronic AC treatment changed the neuronal architecture of the adult hippocampus, possibly by reducing neurogenesis and the extent of the vasculature, independently of neuroinflammation. Such detrimental changes in micromorphometric parameters may explain the hippocampal dysfunction observed after cancer chemotherapy.
Adult
;
Animals
;
Breast Neoplasms
;
Cognition Disorders
;
Cyclophosphamide
;
Cytokines
;
Doxorubicin
;
Drug Therapy
;
Female
;
Hindlimb Suspension
;
Hippocampus
;
Humans
;
Macrophages
;
Memory
;
Mice*
;
Mood Disorders
;
Neurogenesis
;
Neurons
;
Spine
;
Survivors
5.Reference values of hematological and biochemical parameters in young-adult cynomolgus monkey (Macaca fascicularis) and rhesus monkey (Macaca mulatta) anesthetized with ketamine hydrochloride
Bon Sang KOO ; Dong Ho LEE ; Philyong KANG ; Kang Jin JEONG ; Sangil LEE ; Kijin KIM ; Youngjeon LEE ; Jae Won HUH ; Young Hyun KIM ; Sang Je PARK ; Yeung Bae JIN ; Sun Uk KIM ; Ji Su KIM ; Yeonghoon SON ; Sang Rae LEE
Laboratory Animal Research 2019;35(2):39-44
Nonhuman primate models are valuable in biomedical research. However, reference data for clinical pathology parameters in cynomolgus and rhesus monkeys are limited. In the present study, we established hematologic and biochemical reference intervals for healthy cynomolgus and rhesus monkeys anesthetized with ketamine hydrochloride. A total of 142 cynomolgus monkeys (28 males and 114 females) and 42 rhesus monkeys (22 males and 20 females) were selected and analyzed in order to examine reference intervals of 20 hematological and 16 biochemical parameters. The effects of sex were also investigated. Reference intervals for hematological and biochemical parameters were separately established by species (cynomolgus and rhesus) and sex (male and female). No sex-related differences were determined in erythrocyte-related parameters for cynomolgus and rhesus monkey housed in indoor laboratory conditions. Alkaline phosphatase and gamma glutamyltransferase were significantly lower in females than males in both cynomolgus and rhesus monkeys aged 48–96 months. The reference values for hematological and biochemical parameters established herein might provide valuable information for researchers using cynomolgus and rhesus monkeys in experimental conditions for biomedical studies.
6.Evaluation of fecal microbiomes associated with obesity in captive cynomolgus monkeys (Macaca fascicularis)
Bon Sang KOO ; Eun Ha HWANG ; Green KIM ; Hanseul OH ; Yeonghoon SON ; Dongho LEE ; Kyung Seob LIM ; Philyong KANG ; Sangil LEE ; Hwal Yong LEE ; Kang Jin JEONG ; Youngjeon LEE ; Seung Ho BAEK ; Chang Yeop JEON ; Sang Je PARK ; Young Hyun KIM ; Jae Won HUH ; Yeung Bae JIN ; Sun Uk KIM ; Sang Rae LEE ; Jung Joo HONG
Journal of Veterinary Science 2019;20(3):e19-
Microorganisms play important roles in obesity; however, the role of the gut microbiomes in obesity is controversial because of the inconsistent findings. This study investigated the gut microbiome communities in obese and lean groups of captive healthy cynomolgus monkeys reared under strict identical environmental conditions, including their diet. No significant differences in the relative abundance of Firmicutes, Bacteroidetes and Prevotella were observed between the obese and lean groups, but a significant difference in Spirochetes (p < 0.05) was noted. Microbial diversity and richness were similar, but highly variable results in microbial composition, diversity, and richness were observed in individuals, irrespective of their state of obesity. Distinct clustering between the groups was not observed by principal coordinate analysis using an unweighted pair group method. Higher sharedness values (95.81% ± 2.28% at the genus level, and 79.54% ± 5.88% at the species level) were identified among individual monkeys. This paper reports the association between the gut microbiome and obesity in captive non-human primate models reared under controlled environments. The relative proportion of Firmicutes and Bacteroidetes as well as the microbial diversity known to affect obesity were similar in the obese and lean groups of monkeys reared under identical conditions. Therefore, obesity-associated microbial changes reported previously appear to be associated directly with environmental factors, particularly diet, rather than obesity.
Bacteroidetes
;
Diet
;
Environment, Controlled
;
Firmicutes
;
Gastrointestinal Microbiome
;
Haplorhini
;
Macaca fascicularis
;
Methods
;
Microbiota
;
Obesity
;
Prevotella
;
Primates
;
Spirochaetales
7.Increased CD68/TGFβ Co-expressing Microglia/Macrophages after Transient Middle Cerebral Artery Occlusion in Rhesus Monkeys
Hyeon Gu YEO ; Jung Joo HONG ; Youngjeon LEE ; Kyung Sik YI ; Chang Yeop JEON ; Junghyung PARK ; Jinyoung WON ; Jincheol SEO ; Yu Jin AHN ; Keonwoo KIM ; Seung Ho BAEK ; Eun Ha HWANG ; Green KIM ; Yeung Bae JIN ; Kang Jin JEONG ; Bon Sang KOO ; Philyong KANG ; Kyung Seob LIM ; Sun Uk KIM ; Jae Won HUH ; Young Hyun KIM ; Yeonghoon SON ; Ji Su KIM ; Chi Hoon CHOI ; Sang Hoon CHA ; Sang Rae LEE
Experimental Neurobiology 2019;28(4):458-473
The function of microglia/macrophages after ischemic stroke is poorly understood. This study examines the role of microglia/macrophages in the focal infarct area after transient middle cerebral artery occlusion (MCAO) in rhesus monkeys. We measured infarct volume and neurological function by magnetic resonance imaging (MRI) and non-human primate stroke scale (NHPSS), respectively, to assess temporal changes following MCAO. Activated phagocytic microglia/macrophages were examined by immunohistochemistry in post-mortem brains (n=6 MCAO, n=2 controls) at 3 and 24 hours (acute stage), 2 and 4 weeks (subacute stage), and 4, and 20 months (chronic stage) following MCAO. We found that the infarct volume progressively decreased between 1 and 4 weeks following MCAO, in parallel with the neurological recovery. Greater presence of cluster of differentiation 68 (CD68)-expressing microglia/macrophages was detected in the infarct lesion in the subacute and chronic stage, compared to the acute stage. Surprisingly, 98~99% of transforming growth factor beta (TGFβ) was found colocalized with CD68-expressing cells. CD68-expressing microglia/macrophages, rather than CD206⁺ cells, may exert anti-inflammatory effects by secreting TGFβ after the subacute stage of ischemic stroke. CD68⁺ microglia/macrophages can therefore be used as a potential therapeutic target.
Brain
;
Haplorhini
;
Immunohistochemistry
;
Infarction, Middle Cerebral Artery
;
Inflammation
;
Macaca mulatta
;
Magnetic Resonance Imaging
;
Microglia
;
Middle Cerebral Artery
;
Primates
;
Stroke
;
Transforming Growth Factor beta